Convincing evidence has recently accumulated supporting the hypothesis that there is an endogenous neuronal system capable of suppressing pain transmission. This analgesic system can be activated by electrical stimulation of or direct microinjection of opiates into certain brainstem structures. Preliminary experiments demonstrate overlap of sites effective for analgesia with regions relatively rich in opiate receptor and endogenous opiate-like substances (endorphins). The periaqueductal gray of mesencephalon and periventricular gray of diencephalon are consistently effective regions for production of analgesia by electrical stimulation or opiate microinjection. Both opiate receptor and endorphins are present in these regions. Since these regions are not major relay sites for pain transmission, analgesia is most likely produced by the action of these regions on other brain loci. The present experiments will examine the anatomy, pharmacology and physiology of brain sites implicated in analgesia. First, mapping studies will be carried out using autoradiographic and radioimmunoassay techniques for localization of receptor and endorphins. Secondly, we will study the effect upon pain-transmitting and pain-modulating neuronal systems of opiate microinjection into brain sites rich in opiate receptor and enkephalin.